Project Summary/Abstract This project addresses a neglected global disease that is often misdiagnosed yet causes severe morbidity and mortality. In arid regions of the U.S. and Mexico, Borrelia turicatae is the primary species of tick-borne relapsing fever (TBRF) and is transmitted by the soft tick Ornithodoros turicata. Historically considered a disease ofthe impoverished, evidence indicates that B. turicatae is emerging in metropolitan regions of Texas. Just inAustin, TX, the confirmation of B. turicatae in humans in 2017 was the highest in over 40 years. This emergence creates concerns in urban Austin, with more than one million people potentially at risk. Moreover, published evidence indicates the diseases emergence in San Antonio, Dallas, and Austin, three of the top 11 largest cities in the United States. Unfortunately, an clear understanding of the ecology of B. turicatae is vague; primarily the vertebrate hosts that maintain the pathogens. This proposal's hypothesis is that B. turicatae circulates in soft tick populations in urban areas of Austin, TX, and serological detection in rodents will indicate a role of these mammals in maintaining the pathogens in nature. The following Aims are proposed: Aim 1: Understand the potential role of rodents in the enzootic transmission cycle of TBRF. B. turicatae-infected ticks were collected from rodent nests; however, the role of wild rodents as reservoirs for this Borreliaspecies is unknown. The hypothesis of Aim 1 is that the maintenance of B. turicatae in Austin, TX parks involves a tick-rodent infectious cycle. The objective of this aim is to conduct serosurveillance studies with collected wild rodents using highly specific diagnostic antigens, and collect ticks from eight public parks where thepathogens likely circulate. These findings will suggest spirochete propagation in the animals and provide evidence for a role of rodents in maintaining B. turicatae. Aim 2: Assess the level of genetic variation of B. turicatae isolates and O. turicata populations in Austin. The limited number of B. turicatae isolates and a sparsity of collected O. turicata populations has hindered an understanding of the disease's ecology and epidemiology. Thus, the hypothesis of Aim 2 is that B. turicatae variants circulate in nature and are maintained in distinct populations of O. turicata. The objectives of Aim 2 are to (1) obtain novel isolates of B. turicatae from field collected ticks and wild caught rodents, and genetically type the pathogens; and (2) collect distinct populations of O. turicata for an analysis of genetic variance. Understanding the natural history of the disease will lead to better estimates of human health risk. In a region where evidence indicates the emergence of B. turicatae, this project coincides with NIAID's mission to betterunderstand and prevent disease. The results will enable future studies to better assess human health risks indensely populated regions where the pathogens are neglected.